Abstract: Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) are a powerful tool for studying cardiovascular disease and drug screening. However, most current methods of cell culture result in cells resembling fetal myocardium, which is potentially problematic as most forms of cardiovascular disease occur in the adult heart. Disclosed systems and methods include culturing cells in fatty-acid based medium and on patterned growth to produce hiPSC-CMs which mimic adult cardiomyocytes and display a similar hypertrophic response as is observed in cardiovascular disease.

Abstract: Pro-fibrotic signaling potently antagonizes cardiac reprogramming. Inhibition of pro-fibrotic signaling using small molecules that target the transforming growth factor-?/SMAD, or Rho kinase leads to conversion of approximately 60% of fibroblasts into beating cardiomyocytes. Conversely, over-activation of these pro-fibrotic signaling networks inhibits cardiac reprogramming. Using the disclosed methods, fibroblasts are converted to spontaneously contracting cardiomyocytes in less than two weeks.

Abstract: The present invention includes a method of treating and/or preventing metabolic syndrome in a subject in need thereof. In certain embodiments, the method comprises administering to the subject a therapeutically effective amount of a composition that inhibits HDAC11 expression and/or activity, or induces HDAC11 degradation, in the subject.

Abstract: Pro-fibrotic signaling potently antagonizes cardiac reprogramming. Inhibition of pro-fibrotic signaling using small molecules that target the transforming growth factor-?/SMAD, or Rho kinase leads to conversion of approximately 60% of fibroblasts into beating cardiomyocytes. Conversely, over-activation of these pro-fibrotic signaling networks inhibits cardiac reprogramming. Using the disclosed methods, fibroblasts are converted to spontaneously contracting cardiomyocytes in less than two weeks.

Abstract: The present invention provides for methods of treating and cardiac hypertrophy, heart failure, dilated cardiomyopathy or hypertension comprising the use of CaMKII-HDAC binding domains. The present invention discloses not only the fact that CaMKII binds to HDAC4 at a specific site, but that HDAC4 may dimerize with other HDACs. Both events can lead to export of HDACs from the nucleus to the cytoplasm, an event associated with the development of heart disease. Thus the methods of treatment and the screening methods of the present invention are novel attempts to prevent, treat or identify therapies for cardiac hypertrophy, heart failure, dilated cardiomyopathy or hypertension.

Abstract: The present invention provides for methods of treating and cardiac hypertrophy, heart failure, dilated cardiomyopathy or hypertension comprising the use of CaMKII-HDAC binding domains. The present invention discloses not only the fact that CaMKII binds to HDAC4 at a specific site, but that HDAC4 may dimerize with other HDACs. Both events can lead to export of HDACs from the nucleus to the cytoplasm, an event associated with the development of heart disease. Thus the methods of treatment and the screening methods of the present invention are novel attempts to prevent, treat or identify therapies for cardiac hypertrophy, heart failure, dilated cardiomyopathy or hypertension.

Abstract: The present invention relates to cardiac hypertrophy. More particularly, the present invention defines the molecular events linking calcium stimulation to cardiac hypertrophy. More specifically, the present invention shows that Ca2+ stimulation of the hypertrophic response is mediated through an HDAC 4 and 5 interaction with MEF2, and that phosphorylation of HDACs results in loss of HDAC-mediated repression of MEF2 hypertrophic action. Thus, the present invention provides methods and compositions of treating cardiac hypertrophy, as well as methods and compositions for identifying subjects at risk for cardiac hypertrophy. Further provided are methods for the detection of compounds having therapeutic activity toward cardiac hypertrophy.

Abstract: The present invention relates to cardiac hypertrophy. More particularly, the present invention defines the molecular events linking calcium stimulation to cardiac hypertrophy. More specifically, the present invention shows that Ca2+ stimulation of the hypertrophic response is mediated through an HDAC 4 and 5 interaction with MEF2, and that phosphorylation of HDACs results in loss of HDAC-mediated repression of MEF2 hypertrophic action. Thus, the present invention provides methods and compositions of treating cardiac hypertrophy, as well as methods and compositions for identifying subjects at risk for cardiac hypertrophy. Further provided are methods for the detection of compounds having therapeutic activity toward cardiac hypertrophy.

Abstract: The present invention provides for methods of treating and cardiac hypertrophy, heart failure, dilated cardiomyopathy or hypertension comprising the use of CaMKII-HDAC binding domains. The present invention discloses not only the fact that CaMKII binds to HDAC4 at a specific site, but that HDAC4 may dimerize with other HDACs. Both events can lead to export of HDACs from the nucleus to the cytoplasm, an event associated with the development of heart disease. Thus the methods of treatment and the screening methods of the present invention are novel attempts to prevent, treat or identify therapies for cardiac hypertrophy, heart failure, dilated cardiomyopathy or hypertension.

Abstract: The present invention provides for methods of treating and preventing cardiac hypertrophy. Class II HDACs, which are known to participate in regulation of chromatin structure and gene expression, have been shown to have beneficial effects on cardiac hypertrophy. Surprisingly, the present invention demonstrates that HDAC inhibitors inhibit cardiac hypertrophy by inhibiting fetal cardiac gene expression and interfering with sarcomeric organization.

Abstract: The present invention provides for methods of treating and preventing cardiac hypertrophy. Class II HDACs, which are known to participate in regulation of chromatin structure and gene expression, have been shown to have beneficial effects on cardiac hypertrophy. Surprisingly, the present invention demonstrates that HDAC inhibitors inhibit cardiac hypertrophy by inhibiting fetal cardiac gene expression and interfering with sarcomeric organization.

Abstract: The present invention provides methods of treating cardiac hypertrophy by administering a drug that is known to be a non-selective inhibitor of nuclear protein export to patient in need thereof.

Abstract: The present invention provides for methods of treating and preventing cardiac hypertrophy and heart failure. MEF-2 and Class II HDACs have been shown to have a major role in cardiac hypertrophy and heart disease, and inhibition of class II HDAC's has been shown to have a beneficial, anti-hypertrophic effect. The present invention provides a link between MEF-2 and class II HDAC's, a kinase known as PRK. The present invention further demonstrates that inhibitors of PRK inhibit cardiac hypertrophy and heart disease by inhibiting, in part, the fetal cardiac gene expression and cellular reorganization that occurs when MEF-2 dependent transcription is activated.

Abstract: The present invention provides for methods of treating and preventing cardiac hypertrophy. Class II HDACs, which are known to participate in regulation of chromatin structure and gene expression, have been shown to have beneficial effects on cardiac hypertrophy. Surprisingly, the present invention demonstrates that HDAC inhibitors inhibit cardiac hypertrophy by inhibiting fetal cardiac gene expression and interfering with sarcomeric organization.

Abstract: The present invention provides for methods of treating and preventing cardiac hypertrophy and heart failure. MEF-2 and Class II HDACs have been shown to have a major role in cardiac hypertrophy and heart disease, and inhibition of class II HDAC's has been shown to have a beneficial, anti-hypertrophic effect. The present invention provides the link between MEF-2 and class II HDAC's, a kinase known as PKD. The present invention further demonstrates that inhibitors of PKD inhibit cardiac hypertrophy and heart disease by inhibiting, in part, the fetal cardiac gene expression and cellular reorganization that occurs when MEF-2 dependent transcription is inhibited.

Abstract: The present invention relates to cardiac hypertrophy. More particularly, the present invention defines the molecular events linking calcium stimulation to cardiac hypertrophy. More specifically, the present invention shows that Ca2+ stimulation of the hypertrophic response is mediated through an HDAC 4 and 5 interaction with MEF2, and that phosphorylation of HDACs results in loss of HDAC-mediated repression of MEF2 hypertrophic action. Thus, the present invention provides methods and compositions of treating cardiac hypertrophy, as well as methods and compositions for identifying subjects at risk for cardiac hypertrophy. Further provided are methods for the detection of compounds having therapeutic activity toward cardiac hypertrophy.

Abstract: The present invention provides for methods of treating and preventing cardiac hypertrophy. Class II HDACs, which are known to participate in regulation of chromatin structure and gene expression, have been shown to have beneficial effects on cardiac hypertrophy. Surprisingly, the present invention demonstrates that HDAC inhibitors inhibit cardiac hypertrophy by inhibiting fetal cardiac gene expression and interfering with sarcomeric organization.

Abstract: The present invention provides for methods of treating and preventing cardiac hypertrophy. Class II HDACs, which are known to participate in regulation of chromatin structure and gene expression, have been shown to have beneficial effects on cardiac hypertrophy. Surprisingly, the present invention demonstrates that HDAC inhibitors inhibit cardiac hypertrophy by inhibiting fetal cardiac gene expression and interfering with sarcomeric organization.

Abstract: The present invention relates to cardiac hypertrophy. More particularly, the present invention defines the molecular events linking calcium stimulation to cardiac hypertrophy. More specifically, the present invention shows that Ca2+ stimulation of the hypertrophic response is mediated through an HDAC 4 and 5 interaction with MEF2, and that phosphorylation of HDACs results in loss of HDAC-mediated repression of MEF2 hypertrophic action. Thus, the present invention provides methods and compositions of treating cardiac hypertrophy, as well as methods and compositions for identifying subjects at risk for cardiac hypertrophy. Further provided are methods for the detection of compounds having therapeutic activity toward cardiac hypertrophy.

Abstract: The present invention provides for methods of treating and preventing cardiac hypertrophy. Class II HDACs, which are known to participate in regulation of chromatin structure and gene expression, have been shown to have beneficial effects on cardiac hypertrophy. Surprisingly, the present invention demonstrates that HDAC inhibitors inhibit cardiac hypertrophy by inhibiting fetal cardiac gene expression and interfering with sarcomeric organization.